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Older fathers run higher risk of fetal defects

Older fathers are more likely to produce fetuses with chromosomal anomalies that lead to miscarriage or birth defects, shows new research. It was known that older women had a higher risk of such problems, but this is the first research to demonstrate a linear link between age and chromosome anomalies for men.

Scientists at the University Autònoma de Barcelona in Spain studied 200,000 sperm from 18 healthy donors aged 24 to 74 years. The percentage of sperm with double copies of all the chromosomes (diploidy) increases by 17 per cent for every 10 year increase in age, they found.

“Over the age group we found an increase from 0.2 to 0.4 percent in the frequencies of diploidy,” says Josep Egozcue, who led the research. Though this appears small, he told New Scientist, when the researchers checked back with the donors they found that those with the higher frequencies had children with chromosomal anomalies.

Egozcue suggests that men over the age of 55 years should have their sperm checked for chromosomal anomalies before conceiving and should consider freezing their sperm when young.

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Richard Kennedy from the British Fertility Society says that men over 55 are not used as sperm donors anyway due to the quality of their semen. “The incidence of diploidy in older men is probably related to the fact that the pituitary is producing too much follicle stimulating hormone, which affects sperm,” he said.

Checkpoint errors

The scientists used a four-colour fluorescence in-situ hybridisation (FISH) technique, where a fluorescent molecule was attached to the DNA of chromosomes 6, 21, X and Y. The chromosomes for each sperm sample were then counted using an epifluorescence microscope.

“We found that the chromosomes from the older men were not capable of pairing correctly with those in the egg,” says Egozcue says. This leads either to chromosomes being omitted from the fetal cells, or to the cells having three copies of a chromosome. “The incidence of triploidy in spontaneous abortions is as high as 16 per cent,” he adds.

Chris Barratt, an expert in sperm biology from the University of Birmingham, says that as paternal age increases the number of errors at each of the sperm production “checkpoints” increases.

“Although the sperm cell is freshly created, the Sertoli cells, which nurture the sperm are subject to damage over time. Environmental factors like oestrogen mimicking molecules can also deteriorate their quality,” says Barratt.

Sex cells – sperm and egg cells – have 23 single chromosomes each so that a paired set is created when a sperm fertilises an egg. Sperm containing an absent chromosome or diploid can result in birth defects after fertilisation.

The defects include Down’s syndrome, where there are three copies of chromosome 21, or Turner’s syndrome, where there is only one X chromosome. In 80 percent of Turner’s cases, the missing X is the result of defective sperm.